Role of Transcription Factor KlMga2 in the Regulation of Fatty Acids Biosynthesis and Cellular Fitness in Kluyveromyces lactis

Glucose repression is not the predominant regulation of carbon metabolism in K. lactis: regulation of glycolytic (RAG1) and fermentative (KlPDC1) genes is significantly dependent on oxygen availability and also lipid biosynthesis is regulated by hypoxia. We have focused our studies on the role of the hypoxic regulatory gene KlMGA2. We have found that the deletion of KlMGA2 causes the loss of the hypoxic induction of some genes, especially those involved in lipid biosynthesis, and the reduction of transcription level of other metabolic genes. Transcriptional response of lipid biosynthetic genes to low temperature was affected in the mutant strain. The klmga2Δ strain also showed reduced growth rate and rag- phenotype, the latter is typically associated to glycolytic/fermentative defects. This phenotype was suppressed by unsaturated fatty acids (UFAs). The mutant strain also showed defects in mitochondrial morphology, respiration and catalase expression. Hypoxic shift in K. lactis generates induction of transcription of many genes. We showed that the hypoxic regulator KlMga2 has a role in this response. However, KlMga2 is also involved in mitochondrial/respiratory functions and oxidative stress suggesting a general role of this protein in regulating cellular fitness. The suppression by UFAs of the defects of the mutant strain indicate the importance of membrane functions in the mechanisms controlled by KlMga2.